Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

Tegally, Houriiyah; Moir, Monika; Everatt, Josie; Giovanetti, Marta; Scheepers, Cathrine; Wilkinson, Eduan; Subramoney, Kathleen; Makatini, Zinhle; Moyo, Sikhulile; Amoako, Daniel G.; Baxter, Cheryl; Althaus, Christian L.; Anyaneji, Ugochukwu J.; Kekana, Dikeledi; Viana, Raquel; Giandhari, Jennifer; Lessells, Richard J; Maponga, Tongai; Maruapula, Dorcas; Choga, Wonderful T.; Matshaba, Mogomotsi; Mbulawa, Mpaphi B.; Msomi, Nokukhanya; Naidoo, Yeshnee; Pillay, Sureshnee; Sanko, Tomasz Janusz; San, James Emmanuel; Scott, Lesley; Singh, Lavanya; Magini, Nonkululeko A.; Smith-Lawrence, Pamela; Stevens, Wendy; Dor, Graeme; Tshiabuila, Derek; Wolter, Nicole; Preiser, Wolfgang; Treurnicht, Florette K.; Venter, Marietjie; Chiloane, Georginah; McIntyre, Caitlyn; O’Toole, Áine; Ruis, Christopher; Peacock, Thomas P.; Roemer, Cornelius; Pond, Sergei L. Kosakovsky; Williamson, Carolyn; Pybus, Oliver G.; Bhiman, Jinal N.; Glass, Allison; Martin, Darren P.; Jackson, Ben; Rambaut, Andrew; Laguda-Akingba, Oluwakemi; Gaseitsiwe, Simani; Gottberg, Anne von; Oliveira, Túlio de

doi:10.1038/s41591-022-01911-2

Cited by 554 publications

(579 citation statements)

References 42 publications

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“…In 2022 two new sub lineage, BA.4 and BA.5, emerged from the BA.2 lineage in South Africa 4 . Both BA.4/BA.5 share the same mutations in the spike glycoprotein and mainly differ from BA.2 regarding the 69-70del, L452R which was present in the Delta variant, F486V and the reversion to the original amino acid at Q493 4 (Fig. 1 ).…”

Section: Mainmentioning

confidence: 99%

In vitro activity of therapeutic antibodies against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5

Touret

Baronti

Pastorino

et al. 2022

Sci Rep

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The replacement of the Omicron BA.1 variant of SARS-CoV-2 by the BA.2 and the rapid growth of the BA.5 sub lineage, which have both different sets of mutations in the spike glycoprotein, alters the spectrum of activity of therapeutic antibodies currently licensed in the European Union. Using clinical strains of the Omicron BA.2 and BA.5 variants, we compared the neutralising power of monoclonal antibodies against the Omicron BA.1, BA.2 and BA.5 variants, using an ancestral strain (lineage B.1, D614G) and a Delta variant strain as reference. Sotrovimab/Vir-7831 is less active against BA.2 than against BA.1 (fold change reduction ~ 1,4) and even less active against BA.5 (fold change reduction ~ 2.7). Within the Evusheld /AZD7442 cocktail, Cilgavimab/AZD1061 is more active against BA.2 and BA.5 than against BA.1 (fold change increase ~ 32), whilst the very low activity of Tixagevimab/AZD8895 against BA.1 is not enhanced against BA.2 nor BA.5. In total, compared to BA.1, the activity of the Evusheld/AZD7442 is significantly improved against BA.2 while BA.5 is intermediate but closer to BA.2.

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Section: Mainmentioning

confidence: 99%

In vitro activity of therapeutic antibodies against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5

Touret

Baronti

Pastorino

et al. 2022

Sci Rep

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“…SARS-CoV-2 lineages Alpha (B.1.1.7) 15 , Delta (B.1.617.2) 13 3,10 . Alpha Orf6 deletion virus (Alpha ∆Orf6) was achieved by mutation of the first two methionines: M1L (A27216T) and M19L (A27200T).…”

Section: Virusesmentioning

confidence: 99%

Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants

Reuschl

Thorne

Whelan

et al. 2022

Preprint

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SARS-CoV-2 adaptation to its human host is evidenced by the emergence of new viral lineages with distinct genotypic and phenotypic characteristics, termed variants of concern (VOCs). Particular VOCs have become sequentially dominant globally (Alpha, Delta, Omicron) with each evolving independently from the ancestral Wuhan strain. Omicron is notable for its large number of Spike mutations found to promote immune escape and re-infection. Most recently, Omicron BA.4 and BA.5 subvariants have emerged with increasing levels of adaptive immune escape threatening vaccine effectiveness and increasing hospitalisations. Here, we demonstrate that the most recent Omicron variants have enhanced capacity to antagonise or evade human innate immune defenses. We find Omicron BA.4 and BA.5 replication is associated with reduced activation of epithelial innate immune responses versus earlier BA.1 and BA.2 subvariants. We also find enhanced expression of innate immune antagonist proteins Orf6 and N, similar to Alpha, suggesting common pathways of human adaptation and linking VOC dominance to improved innate immune evasion. We conclude that Omicron BA.4 and BA.5 have combined evolution of antibody escape with enhanced antagonism of human innate immunity to improve transmission and possibly reduce immune protection from severe disease.

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“…During this period, national sequencing showed that Omicron BA.4/5 was responsible for >90% of genomes 8 . Of these participants, 30 had matched nasal swabs available.…”

Section: Plasma From Individuals Infected During the Fifth Wave Of Th...mentioning

confidence: 99%

SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1

Richardson

Motlou

Mescht

et al. 2022

Preprint

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SARS-CoV-2 variants of concern (VOCs) differentially trigger neutralizing antibodies with variable cross-neutralizing capacity. Here we show that unlike SARS-CoV-2 Omicron BA.1, which triggered neutralizing antibodies with limited cross-reactivity, BA.4/5 infection triggers highly cross-reactive neutralizing antibodies. Cross-reactivity was observed both in the absence of prior vaccination and also in breakthrough infections following vaccination. This suggests that next-generation vaccines incorporating BA.4, which is spreading globally, might result in enhanced neutralization breadth.

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Emergence of SARS-CoV-2 Omicron lineages BA.4 and BA.5 in South Africa

Cited by 554 publications

References 42 publications

In vitro activity of therapeutic antibodies against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5

In vitro activity of therapeutic antibodies against SARS-CoV-2 Omicron BA.1, BA.2 and BA.5

Evolution of enhanced innate immune suppression by SARS-CoV-2 Omicron subvariants

SARS-CoV-2 BA.4 infection triggers more cross-reactive neutralizing antibodies than BA.1

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